Study of Sacituzumab Govitecan in Participants With Urothelial Cancer That Cannot Be Removed or Has Spread (TROPHY U-01)

August 31, 2026 updated by: Gilead Sciences

A Phase II Open-Label Study of Sacituzumab Govitecan in Unresectable Locally Advanced/Metastatic Urothelial Cancer

The objective of this study is to evaluate the efficacy and safety of sacituzumab govitecan-hziy monotherapy and with novel combinations in participants with metastatic urothelial cancer (mUC).

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Non-Randomized for Cohorts 1,2,3, and 4; Randomized for Cohorts 5, 6, and 7. Cohort 5 has been cancelled, effective December 2023.

Study Type

Interventional

Enrollment (Actual)

502

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Besançon, France, 25000
        • Centre Hospitalier Regional Universitaire (CHRU) de Besancon, Hopital Jean Minjoz
      • Bordeaux, France, 33000
        • Hopital Saint Andre (CHU de Bordeaux)
      • Brest, France, 29200
        • Centre Hospitalier Regional Universitaire Brest
      • Clermont-Ferrand, France, 63011
        • Centre Jean Perrin
      • La Roche-sur-Yon, France, 85925
        • Centre Hospitalier Departmental (CHD) Vendee
      • Lille, France, 59000
        • Centre Oscar Lambret
      • Lyon, France, 69373
        • Centre Léon Bérard
      • Marseille, France, 13273
        • Institut Paoli Calmettes
      • Nice, France, 06189
        • Centre Antoine Lacassagne
      • Nîmes, France, 30029
        • Centre Hospitalier Universitaire De Nimes - Hopital Universitaire Caremeau
      • Paris, France, 75014
        • Hôpital Cochin
      • Paris, France, 75013
        • Groupement Hospitalier Pitie-Salpetriere
      • Paris, France, 33000
        • Hopital European Georges-Pompidou (HEGP)
      • Rennes, France, 35042
        • Centre Eugène Marquis
      • Rennes, France, 35000
        • Centre Hospitalier Prive Saint-Gregoire
      • Rouen, France, 76031
        • CHU de Rouen
      • Strasbourg, France, 67200
        • Hospitaux Universitaires de Strasbourg - Hopital Civil
      • Suresnes, France, 92150
        • Hospital Foch
      • Toulouse, France, 31059
        • Institut Claudius Regaud
      • Vandœuvre-lès-Nancy, France, 54519
        • Institut de cancerologie de Lorraine
      • Villejuif, France, 94800
        • Institut Gustave Roussy
  • Germany
      • Duisburg, Germany, 47179
        • Urologicum Duisburg
      • Frankfurt, Germany, 60389
        • Centrum fur Hamatologie und Onkologie Bethanien
      • Frankfurt, Germany, 60590
        • Universitätsklinikum Frankfurt, Klinik für Urologie
      • Freiburg im Breisgau, Germany, 79106
        • Universitätsklinikum Freiburg
      • Hamburg, Germany, 20246
        • Universitätsklinikum Hamburg-Eppendorf
      • Heidelberg, Germany, 69120
        • University Hospital Heidelberg
      • Herne, Germany, 44625
        • Marien Hospital Herne
      • Jena, Germany, 07743
        • Universitätsklinikum Jena
      • Koblenz, Germany, 56068
        • Institut für Versorgungsforschung in der Onkologie
      • Magdeburg, Germany, 39120
        • Universitätsklinikum Magdeburg
      • Mainz, Germany, 55131
        • Universitatsklinikum Carl Gustav Carus an der TU Dresden
      • München, Germany, 81675
        • Klinikum rechts der Isar der Technischen Universität München, Urologische Klinik und Poloklinik
      • Münster, Germany, 48149
        • Universitatsklinikum Munster, Klinik fur Urologie und Kinderurologie
      • Regensburg, Germany, 93053
        • Universitat Regensburg
      • Tübingen, Germany, 72076
        • Universitatsklinikum Tubingen, Klinik fur Urologie
  • Greece
      • Athens, Greece, 11526
        • Henry Dunant Hospital Center, 4th Oncology Department
      • Ioannina, Greece, 45500
        • University General Hospital of Ioannina, Oncology Department
      • Marousi, Greece, 15125
        • Athens Medical Center, Oncology Department
      • Pátrai, Greece, 26335
        • General Hospital of Patras Agios Andreas
      • Volos, Greece, 38333
        • Anassa General Clinic, Oncology-Chemotherapy Department
  • Italy
      • Arezzo, Italy, 52100
        • Ospedale San Donato
      • Aviano, Italy, 33081
        • Centro di Riferimento Oncologico IRCCS
      • Cremona, Italy, 26100
        • ASST Cremona
      • Genoa, Italy, 16132
        • Ospedale Policlinico San Martino IRCCS
      • Meldola, Italy, 47014
        • Istituto Romagnolo per Io Studio dei Tumori (IRST) "Dino Amadori"
      • Milan, Italy, 20133
        • Fondazione IRCCS Istituto Nazionale dei Tumori
      • Milan, Italy, 20133
        • IRCCS Ospedale San Raffaele
      • Novara, Italy, 28100
        • Azienda Ospedaliero Universitaria Maggiore della Carità
      • Padova, Italy, 35128
        • Istituto Oncologico Veneto IRCCS - Ospedale Busonera
      • Pisa, Italy, 56126
        • Azienda Ospedaliero-Universitaria Pisana
      • Roma, Italy, 00144
        • Instituto Nazionale Tumori Regina Elena - IFO
      • Terni, Italy, 05100
        • Azienda Ospedaliera Santa Maria di Temi
      • Verona, Italy, 37126
        • Centro Ricerche Cliniche di Verona srl
  • South Korea
      • Daegu, South Korea, 42601
        • Keimyung University Dongsan Hospital
      • Daegu, South Korea, 41404
        • Kyungpook National University Chilgok Hospital
      • Goyang-si, South Korea, 10408
        • National Cancer Center
      • Gwangju, South Korea, 61469
        • Chonnam National University Hospital
      • Hwasun, South Korea, 519-763
        • Chonnam National University Hwasun Hospital
      • Seongbuk-Gu, South Korea
        • Korea University - Anam Hospital
      • Seoul, South Korea, 03080
        • Seoul National University Hospital
      • Seoul, South Korea, 06351
        • Samsung Medical Center
      • Seoul, South Korea, 03722
        • Yonsei University Health System, Severance Hospital
      • Seoul, South Korea, 5505
        • Asan Medical Center
      • Seoul, South Korea, 07061
        • SMG-SNU Boramae Medical Center
      • Suwon, South Korea, 16247
        • The Catholic University Of Korea, St. Vincent's Hospital
      • Wŏnju, South Korea, 26426
        • Yonsei University - Wonju Severance Christian Hospital
      • Yangsan, South Korea, 50612
        • Pusan National University Yangsan Hospital
  • Spain
      • Badalona, Spain, 08916
        • Institut Catala d'Oncologia Badalona - Hospital Universitari Germans Trias i Pujol
      • Barcelona, Spain, 08003
        • Hospital del Mar
      • Barcelona, Spain, 08023
        • Hospital Clínic de Barcelona
      • Barcelona, Spain, 08035
        • CEIC Hospital Vall d'Hebron
      • Córdoba, Spain, 14004
        • Hospital Universitario Reina Sofia
      • Las Palmas, Spain, 35016
        • Complejo Hospitalario Universitario Insular Materno Infantil
      • Madrid, Spain, 28034
        • Hospital Universitario Ramón y Cajal
      • Madrid, Spain, 28041
        • Hospital Universitario 12 de Octubre
      • Madrid, Spain, 28046
        • Hospital Universitario La Paz
      • Madrid, Spain, 28040
        • Hospital Universitario Clínico San Carlos
      • Madrid, Spain, 28033
        • MD Anderson Cancer Centre
      • Majadahonda, Spain, 28222
        • Hospital Universitario Puera de Hierro Majadahonda
      • Manresa, Spain, 08243
        • Hospital Sant Joan De Deu
      • Ourense, Spain, 32005
        • Complejo Hospitalario de Ourense
      • Santander, Spain, 39008
        • Hospital Universitario Marqués de Valdecilla
      • Santiago de Compostela, Spain, 15706
        • Complejo Hospitalario Universitario de Santiago
      • Valencia, Spain, 46010
        • Hospital Clínico Universitario de Valencia
      • Zaragoza, Spain, 50009
        • Hospital Universitario Miguel Servet
  • Turkey (Türkiye)
      • Ankara, Turkey (Türkiye), 06550
        • Ankara Sehir Hastanesi
      • Diyarbakır, Turkey (Türkiye), 21280
        • Dicle Universitesi Tip Fakultesi Hastanesi
      • Edrine, Turkey (Türkiye), 22030
        • Trakya Universitesi Saglik Arastirma ve Uygulama Merkezi
      • Istanbul, Turkey (Türkiye), 34214
        • Medipol Mega Üniversite Hastanesi
      • Istanbul, Turkey (Türkiye), 34098
        • Istanbul Universitesi Cerrahpasa Tip Fakultesi Hastanesi
      • Istanbul, Turkey (Türkiye), 34722
        • T.C. Saglik Bakanligi Goztepe Prof Dr. Suleyman Yalcin Sehir Hastanesi
      • Izmir, Turkey (Türkiye), 35575
        • Izmir Medical Point Hastanesi, Medikal Onkoloji Departmant
      • Seyhan, Turkey (Türkiye), 01250
        • Baskent Universitesi Adana Dr.Turgut Noyan Uygulama ve Arastima Merkezi
  • United Kingdom
      • Birmingham, United Kingdom, B9 5SS
        • University Hospitals Birmingham Nhs Foundation Trust
      • London, United Kingdom, E1 1BB
        • Barts Health NHS Trust
      • Northwood, United Kingdom, HA6 2JW
        • East and North Hertfordshire NHS Trust
      • Surrey, United Kingdom, SM2 5PT
        • The Royal Marsden NHS Foundation Trust
  • United States
    • Arizona
      • Tucson, Arizona, United States, 85719
        • The University of Arizona Cancer Center-North Campus
    • California
      • San Francisco, California, United States, 94158
        • University of California San Francisco
    • Colorado
      • Littleton, Colorado, United States, 80120
        • Rocky Mountain Cancer Centers
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Smilow Cancer Hospital at Yale-New Haven
    • Florida
      • Miami Beach, Florida, United States, 33140
        • Mount Sinai Comprehensive Cancer Center
      • Pensacola, Florida, United States, 32503
        • Woodlands Medical Specialists, PA
      • Tampa, Florida, United States, 33612
        • Moffitt Cancer Center
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Winship Cancer Institute, Emory University
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago Medical Center
      • Chicago, Illinois, United States, 60612
        • University of Illinois Cancer Center
      • Springfield, Illinois, United States, 62702
        • Southern Illinois University School of Medicine, Simmons Cancer Institute
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • Norton Cancer Institute, Downtown
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan
      • Detroit, Michigan, United States, 48201
        • Karmanos Cancer Institute
    • New Mexico
      • Albuquerque, New Mexico, United States, 87109
        • Precision Cancer Research / New Mexico Oncology & Hematology Consultants
    • New York
      • Buffalo, New York, United States, 14263
        • Roswell Park Cancer Institute
      • New York, New York, United States, 10016
        • Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
      • New York, New York, United States, 10065
        • Drug Shipping Address: New York-Presbyterian Hospital
      • Stony Brook, New York, United States, 11794
        • Stony Brook Cancer Center
    • Pennsylvania
      • Easton, Pennsylvania, United States, 18045
        • St. Luke's Hosptial - Bethlehem Campus
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of Southern Carolina
    • Tennessee
      • Knoxville, Tennessee, United States, 37932
        • Thompson Oncology Group - Knoxville West
      • Nashville, Tennessee, United States, 37232
        • Henry-Joyce Cancer Clinic
    • Texas
      • Houston, Texas, United States, 77030
        • Houston Methodist Hospital, Houston Methodist Cancer Center
      • San Antonio, Texas, United States, 78229
        • Mays Cancer Center
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • University of Utah - Huntsman Cancer Hospital (IP Shipping Address)
    • Virginia
      • Hampton, Virginia, United States, 23666
        • Virginia Oncology Associates
      • Roanoke, Virginia, United States, 24014
        • Oncology Hematology Associates of Southwest Virginia, Inc., DBA Blue Ridge Cancer Care
    • Washington
      • Seattle, Washington, United States, 98109
        • Seattle Cancer Care Alliance
    • Wisconsin
      • Madison, Wisconsin, United States, 53705
        • University of Wisconsin Clinical Science Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria:

Inclusion Criteria for All Cohorts:

  • Female or male individuals, ≥ 18 years of age (19 Years old for South Korea).
  • Eastern Cooperative Oncology Group (ECOG) Performance status score of 0 or 1.
  • Adequate renal and hepatic function.
  • Adequate hematologic parameters without transfusional support.
  • Individuals must have a 3-month life expectancy.

Additional Inclusion Criteria for Cohorts 1 to 6:

  • Cohort 1: Have had progression or recurrence of urothelial cancer following receipt of platinum-containing regimen (cisplatin or carboplatin):

    1. Received a first-line platinum-containing regimen in the metastatic setting or for inoperable locally advanced disease;
    2. Or received neo/adjuvant platinum-containing therapy for localized muscle-invasive urothelial cancer, with recurrence/progression ≤12 months following completion of therapy.
  • Cohort 1: In addition to above criterion, have had progression or recurrence of urothelial cancer following receipt of an Anti-programmed Cell Death Protein 1 (anti-PD-1)/ Anti-programmed Death Ligand 1 (PD-L1) therapy.
  • Cohort 2: Were ineligible for platinum-based therapy for first line metastatic disease and have had progression or recurrence of urothelial cancer after a first-line therapy for metastatic disease with anti-PD-1/PD-L1 therapy. Individual may not have received any platinum for treatment of recurrent, metastatic or advanced disease.
  • Cohort 3: Progression or recurrence of UC following a platinum containing regimen in the metastatic setting, or progression or recurrence of UC within 12 months of completion of platinum-based therapy as neoadjuvant or adjuvant therapy.
  • Cohort 4: Individual has not received any platinum-based chemotherapy in the metastatic or unresectable locally advanced setting. Creatinine clearance of at least 50 mL/min calculated by Cockcroft-Gault formula or another validated tool. For individuals receiving cisplatin at 70 mg/m^2 on Day 1 of every 21-day cycle, a creatinine clearance of least 60 mL/min calculated by Cockcroft -Gault formula or another validated tool is required. Individuals with creatinine clearance between 50 to 59 mL/min are to receive a split dose of cisplatin (35 mg/m^2 Day 1 and Day 8 of every 21-day cycle).
  • Cohorts 4, 5, 6: Archival tumor tissue comprising muscle-invasive or metastatic urothelial carcinoma, or a biopsy of metastatic urothelial carcinoma.
  • Cohort 5: Individuals received at least 4 cycles and no more than 6 cycles of GEM + cisplatin. No other chemotherapy regimens are allowed in this cohort, with the exception of prior adjuvant or neoadjuvant systemic therapy with curative intent after > 12 months from completion of therapy.
  • No evidence of progressive disease following completion of first-line chemotherapy (ie, CR, PR, or SD per RECIST v1.1 guidelines as per investigator).
  • Treatment-free interval of 4 to 10 weeks since the last dose of chemotherapy.
  • Cohort 6: Cis-ineligible and no prior therapy for metastatic disease or for unresectable locally advanced disease. Checkpoint inhibitor therapy naïve or >12 months from completion of adjuvant therapy are permitted.
  • Cohorts 4 and 6: Have measurable disease by CT or MRI as per RECIST 1.1 criteria. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
  • Cohorts 1, 2, 3 and 5: Creatinine clearance ≥ 30 mL/min as calculated by the Cockcroft-Gault formula unless otherwise specified

Additional Inclusion Criteria for Cohort 7:

  • No prior systemic therapy for locally advanced or metastatic UC. Therapy in the curative setting is allowed provided recurrence is > 12 months since the last dose of systemic therapy.
  • Archival tumor tissue comprising muscle-invasive or metastatic urothelial carcinoma, or a biopsy of metastatic urothelial carcinoma.
  • Have measurable disease by CT or MRI as per RECIST 1.1 criteria. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.

Key Exclusion Criteria:

Exclusion Criteria for All cohorts:

  • Females who are pregnant or lactating.
  • Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
  • Has an active second malignancy.
  • Has known active Hepatitis B or Hepatitis C.
  • Has other concurrent medical or psychiatric conditions.
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
  • Has an active second malignancy.

Additional Exclusion Criteria for Cohorts 1 to 6:

  • For Cohort 5: Alopecia, sensory neuropathy Grade ≤2 is acceptable, or other Grade << 2 adverse events not constituting a safety risk based on the investigator's judgment are acceptable.
  • Cohort 3: Has received anti-PD-1/PD-L1 therapy previously.
  • Cohorts 3 to 6: Has an active autoimmune disease that required systemic treatment in past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
  • Cohorts 3 to 6: Has received a live vaccine within 30 days prior to the first dose of study drug(s), has history or evidence of interstitial lung disease (ILD) or non-infectious pneumonitis.
  • Cohort 4: Refractory to platinum (i.e., relapsed ≤ 12 months after completion of chemotherapy) in the neoadjuvant/adjuvant setting.
  • Cohorts 4, 5, and 6: For individuals who received prior CPI, a treatment-free interval >12 months between the last treatment administration and the date of recurrence is required.

Additional Exclusion Criteria for Cohort 7:

  • Have had a prior anticancer therapy within 12 months prior to C1D1 or prior radiation therapy within 2 weeks prior to C1D1. Individuals participating in observational studies are eligible. Use of other investigational drugs (drugs not marketed for any indication) within 28 days or 5 half-lives (whichever is longer) of first dose of investigational product.
  • Have a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
  • Have a Child-Pugh score of B or C.
  • Individuals with uncontrolled diabetes.
  • Have active keratitis or corneal ulcerations.
  • Participants with ongoing sensory or motor neuropathy Grade ≥ 2.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort 1: Sacituzumab Govitecan-hziy (SG)
Participants with urothelial cancer (UC) previously treated with platinum-based and/or checkpoint inhibitors (CPIs) will receive SG 10 mg/kg intravenously (IV) on Days 1 and 8 of a 21-day cycle.
Drug: Sacituzumab Govitecan-hziy
Administered intravenously.
Other Names:
  • IMMU-132
  • Trodelvy™
Experimental: Cohort 2: SG
Participants with UC who are ineligible for platinum-based therapy and failed therapy with previous immune CPI therapy will receive SG 10 mg/kg intravenously on Days 1 and 8 of a 21-day cycle.
Drug: Sacituzumab Govitecan-hziy
Administered intravenously.
Other Names:
  • IMMU-132
  • Trodelvy™
Experimental: Cohort 3: SG + Pembrolizumab
Participants who have had progression or recurrence of UC following a platinum-containing regimen in the metastatic setting, or progression or recurrence of UC within 12 months of completion of platinum-based therapy as neoadjuvant or adjuvant therapy will receive SG 10 mg/kg intravenously on Days 1 and 8 of a 21-day cycle and pembrolizumab at the standard approved dose (200 mg) only on Day 1 of a 21-day cycle. Lower doses of SG may be tested based on dose-limiting toxicities (DLTs) observed to determine the Recommended Phase 2 Dose (RP2D) of SG in combination with pembrolizumab.
Drug: Sacituzumab Govitecan-hziy
Administered intravenously.
Other Names:
  • IMMU-132
  • Trodelvy™
Drug: Pembrolizumab
Administered per package insert
Other Names:
  • KEYTRUDA®
Experimental: Cohort 4: SG + Cisplatin + Avelumab (Dose Escalation Phase)
Participants with UC who have never received therapy with platinum in the metastatic setting or for unresectable locally advanced disease will first receive cisplatin (either at 70 mg/m^2 on Day 1 of a 21-day cycle or at a split dose of 35 mg/m^2 on Days 1 and 8 of a 21-day cycle with a maximum body surface area of 2) and sacituzumab govitecan-hziy with maximum dose of 10 mg/kg intravenously on Days 1 and 8 of a 21-day cycle for up to 6 cycles. Based on DLTs observed, two additional lower doses may be tested to determine RP2D of sacituzumab govitecan-hziy in combination with cisplatin. If premature termination of 1 agent occurs due to toxicity, the other agent may be continued to complete up to 6 cycles of therapy. For participants who have not progressed, maintenance therapy will begin with infusions of avelumab 800 mg every 2 weeks beginning on Cycle 1, Day 1 and every 2 weeks thereafter and sacituzumab govitecan-hziy 10 mg/kg on Days 1 and 8 every 21 days.
Drug: Sacituzumab Govitecan-hziy
Administered intravenously.
Other Names:
  • IMMU-132
  • Trodelvy™
Drug: Cisplatin
Administered per package insert
Drug: Avelumab
Administered per package insert
Other Names:
  • BAVENCIO®
Experimental: Cohort 4: SG + Cisplatin + Zimberelimab (ZIM) (Dose Expansion Phase)
Participants with UC who have never received therapy with platinum in the metastatic setting or for unresectable locally advanced disease will first receive cisplatin (either at 70 mg/m^2 on Day 1 of a 21-day cycle or at a split dose of 35 mg/m^2 on Days 1 and 8 of a 21-day cycle with a maximum body surface area of 2) and sacituzumab govitecan-hziy with maximum dose of 10 mg/kg intravenously on Days 1 and 8 of a 21-day cycle for up to 6 cycles. If premature termination of 1 agent occurs due to toxicity, the other agent may be continued to complete up to 6 cycles of therapy. For participants who have not progressed, maintenance therapy will begin with infusions of sacituzumab govitecan-hziy 10 mg/kg on Days 1 and 8 every 21 days and zimberelimab 360 mg every 3 weeks (Day 1 of a 21-day cycle).
Drug: Sacituzumab Govitecan-hziy
Administered intravenously.
Other Names:
  • IMMU-132
  • Trodelvy™
Drug: Cisplatin
Administered per package insert
Drug: Zimberelimab
Administered intravenously
Experimental: Cohort 5 (Arm 1): SG + ZIM
Participants in Cohort 5 will have completed 4 to 6 cycles of gemcitabine (GEM) + cisplatin therapy without PD prior to study entry. The safety lead-in will be conducted, in 6 to 8 participants (treated with SG 10 mg/kg IV on Day 1 and Day 8 of a 21-day cycle + ZIM 360 mg IV every 3 weeks on a 21-day cycle). Upon completion of the safety lead-in, participants will receive SG 10 mg/kg IV on Days 1 and 8 of a 21-day cycle followed by ZIM 360 mg IV, every 3 weeks (Q3W) (Day 1 of a 21-day cycle) until PD, unacceptable toxicity, or loss of clinical benefit. participants who must discontinue 1 agent may continue the other until PD, unacceptable toxicity, or loss of clinical benefit.
Drug: Sacituzumab Govitecan-hziy
Administered intravenously.
Other Names:
  • IMMU-132
  • Trodelvy™
Drug: Zimberelimab
Administered intravenously
Experimental: Cohort 5 (Arm 2): Avelumab
Participants in Cohort 5 will have completed 4 to 6 cycles of gemcitabine (GEM) + cisplatin therapy without PD prior to study entry. The safety lead-in will be conducted, in 6 to 8 participants (treated with SG 10 mg/kg IV on Day 1 and Day 8 of a 21-day cycle + ZIM 360 mg IV every 3 weeks on a 21-day cycle). Upon completion of the safety lead-in, participants will be randomized to receive avelumab 800 mg IV every 2 weeks (Q2W) until PD, unacceptable toxicity, or loss of clinical benefit.
Drug: Avelumab
Administered per package insert
Other Names:
  • BAVENCIO®
Experimental: Cohort 5 (Arm 3): ZIM

Participants in Cohort 5 will have completed 4 to 6 cycles of gemcitabine (GEM) + cisplatin therapy without PD prior to study entry. The safety lead-in will be conducted, in 6 to 8 participants (treated with SG 10 mg/kg IV on Day 1 and Day 8 of a 21-day cycle + ZIM 360 mg IV every 3 weeks on a 21-day cycle).

Upon completion of the safety lead-in, participants will be randomized to receive ZIM 360 mg IV Q3W (Day

1 of a 21-day cycle) until PD, unacceptable toxicity, or loss of clinical benefit.
Drug: Zimberelimab
Administered intravenously
Experimental: Cohort 6 (Arm 1): SG
Upon completion of the safety lead-in, participants in Cohort 6 will be randomized and SG will be administered in cisplatin-ineligible participants who have never received therapy in the metastatic setting or for unresectable locally advanced disease. Treatment may be discontinued at any time, but participants will continue to be followed for tumor response until progression is documented, and alternate therapy is initiated. If participants discontinue therapy before evidence of radiologic progression, imaging should continue until radiologic progression is documented, if feasible.
Drug: Sacituzumab Govitecan-hziy
Administered intravenously.
Other Names:
  • IMMU-132
  • Trodelvy™
Experimental: Cohort 6 (Arm 2): SG + ZIM
Upon completion of the safety lead-in, participants in Cohort 6 will be randomized and SG in combination with ZIM will be administered in cisplatin-ineligible participants who have never received therapy in the metastatic setting or for unresectable locally advanced disease. The standard approved dose of SG will be used in combination with ZIM. Treatment may be discontinued at any time, but participants will continue to be followed for tumor response until progression is documented or alternate therapy is initiated. If participants discontinue therapy before evidence of radiologic progression, imaging should continue until radiologic progression is documented, if feasible.
Drug: Sacituzumab Govitecan-hziy
Administered intravenously.
Other Names:
  • IMMU-132
  • Trodelvy™
Drug: Zimberelimab
Administered intravenously
Experimental: Cohort 6 (Arm 3): SG + ZIM + Domvanalimab (DOM)
Upon completion of the safety lead-in, participants in Cohort 6 will be randomized and SG in combination with ZIM and DOM will be administered in cisplatin-ineligible participants who have never received therapy in the metastatic setting or for unresectable locally advanced disease.
Drug: Sacituzumab Govitecan-hziy
Administered intravenously.
Other Names:
  • IMMU-132
  • Trodelvy™
Drug: Zimberelimab
Administered intravenously
Drug: Domvanalimab
Administered intravenously
Experimental: Cohort 6 (Arm 4): Carboplatin (CARBO) + Gemcitabine (GEM)
Upon completion of the safety lead-in, participants in Cohort 6 will be randomized and CARBO in combination with GEM will be administered in cisplatin-ineligible participants who have never received therapy in the metastatic setting or for unresectable locally advanced disease. Participants without disease progression as assessed by the investigator after completion of 4 to 6 cycles of therapy may continue with maintenance therapy (avelumab 800 mg every 2 weeks) until loss of clinical benefit.
Drug: Avelumab
Administered per package insert
Other Names:
  • BAVENCIO®
Drug: Carboplatin
Administered per package insert
Drug: Gemcitabine
Administered per package insert
Experimental: Cohort 7 (Phase 1: Safety Lad-in and Dose Expansion): SG + Enfortumab Vedotin (EV) + ZIM

In the safety lead-in phase, participants will receive a starting dose level of SG 7.5 mg/kg IV and starting dose level of EV 1.25 mg/kg IV will be administered on Days 1 and 8 of each 21-day cycle and ZIM 360 mg IV will be administered on Day 1 of each 21-day cycle.

In dose-expansion, participants will receive SG IV and EV IV at the RP2Ds on Days 1 and 8 of each 21-day cycle and ZIM 360 mg IV on Day 1 of each 21-day cycle.
Drug: Sacituzumab Govitecan-hziy
Administered intravenously.
Other Names:
  • IMMU-132
  • Trodelvy™
Drug: Zimberelimab
Administered intravenously
Drug: Enfortumab Vedotin
Administered intravenously
Experimental: Cohort 7 (Phase 2: Arm 1): SG + EV + ZIM
Upon completion of the Cohort 7 dose-expansion phase, participants will receive SG IV at the RP2D in combination with EV IV at the RP2D, and ZIM 360 mg IV until PD, unacceptable toxicity, or loss of clinical benefit.
Drug: Sacituzumab Govitecan-hziy
Administered intravenously.
Other Names:
  • IMMU-132
  • Trodelvy™
Drug: Zimberelimab
Administered intravenously
Drug: Enfortumab Vedotin
Administered intravenously
Experimental: Cohort 7 (Phase 2: Arm 2): EV + ZIM
Upon completion of the Cohort 7 dose-expansion phase, participants will receive EV 1.25 mg/kg IV and ZIM 360 mg IV.
Drug: Zimberelimab
Administered intravenously
Drug: Enfortumab Vedotin
Administered intravenously
Experimental: Cohort 7 (Phase 2: Arm 3): Optional Dose Optimization SG + EV + ZIM
Upon completion of the Cohort 7 dose-expansion phase, participants will receive SG IV at 1 dose level below the RP2D in combination with EV 1.25 mg/kg IV and ZIM 360 mg IV.
Drug: Sacituzumab Govitecan-hziy
Administered intravenously.
Other Names:
  • IMMU-132
  • Trodelvy™
Drug: Zimberelimab
Administered intravenously
Drug: Enfortumab Vedotin
Administered intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Rate (ORR) Based on Central Review by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Criteria (Cohorts 1 to 4 and 6)
Time Frame: Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))
ORR will be defined as the rate of the best overall response as Complete Response (CR) or Partial Response (PR) and based on central review by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) criteria.
Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))
Progression free survival (PFS) Based on Central Review by RECIST 1.1 criteria (Cohort 5)
Time Frame: Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))
PFS will be defined as the time from first dose until objective tumor progression, as assessed based on central review, or death, whichever comes first.
Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))
ORR Based on Investigator Review by RECIST 1.1 Criteria (Cohort 7)
Time Frame: Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))
ORR will be defined as the rate of the best overall response as Complete Response (CR) or Partial Response (PR) and based on investigator review by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) criteria.
Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))
Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) (Cohort 7)
Time Frame: First dose date up to last dose date plus 30 days (approximately 3 years)
First dose date up to last dose date plus 30 days (approximately 3 years)
Percentage of Participants Experiencing any Clinically Significant Laboratory Abnormalities (Cohort 7)
Time Frame: First dose date up to last dose date plus 30 days (approximately 3 years)
First dose date up to last dose date plus 30 days (approximately 3 years)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Rate (ORR)
Time Frame: Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))
ORR will be defined as the rate of the best overall response as CR or PR and based on investigator review by RECIST 1.1 criteria for cohorts 3, 4, 6, and 7. ORR will also be evaluated based on investigator review by Modified RECIST 1.1 for Immune-Based Therapeutics (iRECIST 1.1) for Cohorts 3, 4, 6, and 7.
Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))
Duration of Response (DOR)
Time Frame: Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))
DOR will be calculated from the date of the first evaluation showing documented response, PR, or CR, to the date of the first disease progression or death and based on central and investigator review by RECIST 1.1 criteria for all cohorts. DOR will also be evaluated based on investigator review by iRECIST 1.1 for Cohorts 3, 4, 6, and 7.
Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))
Progression-Free Survival (PFS)
Time Frame: Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))
PFS is defined as the time from the first dose (Cohorts 1 through 4) or randomization date (Cohorts 5 through 7) until objective tumor progression,or death, whichever comes first and based on central and investigator review by RECIST 1.1 criteria for all cohorts. PFS will also be evaluated based on investigator review by iRECIST 1.1 for Cohorts 3, 4, 6, and 7.
Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))
Overall Survival (OS)
Time Frame: Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))
OS will be measured from the date of first dose (Cohorts 1 through 4) or randomization date (Cohorts 5 through 7) to death from any cause.
Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))
Clinical Benefit Rate (CBR)
Time Frame: Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))
CBR is defined as CR + PR + Stable Disease (SD) for at least 6 months and based on central and investigator review by RECIST 1.1 criteria for Cohorts 3, 4, 6, and 7. CBR will also be evaluated based on investigator review by iRECIST 1.1 for Cohorts 3, 4, 6, and 7.
Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))
Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) (Cohorts 3, 4, 5, and 6)
Time Frame: First dose date up to last dose date plus 30 days (approximately 3 years)
First dose date up to last dose date plus 30 days (approximately 3 years)
Percentage of Participants Experiencing any Clinically Significant Laboratory Abnormalities (Cohorts 3, 4, 5, and 6)
Time Frame: First dose date up to last dose date plus 30 days (approximately 3 years)
First dose date up to last dose date plus 30 days (approximately 3 years)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gilead Sciences

Collaborators

Merck KGaA, Darmstadt, Germany

Investigators

  • Study Director: Gilead Study Director, Gilead Sciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 13, 2018

Primary Completion (Estimated)

April 1, 2030

Study Completion (Estimated)

April 1, 2030

Study Registration Dates

First Submitted

April 26, 2018

First Submitted That Met QC Criteria

June 5, 2018

First Posted (Actual)

June 6, 2018

Study Record Updates

Last Update Posted (Actual)

September 1, 2026

Last Update Submitted That Met QC Criteria

August 31, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IMMU-132-06
  • 2023 (U.S. NIH Grant/Contract: GRAMMY Museum Foundation)
  • 2023-508302-24 (Other Identifier: European Medicines Agency)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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